Skeletal muscle requires large numbers of factors delivered by the peripheral circulation to sustain its high metabolic rate, and extensive growth during development. We hypothesize that there are a series of naturally occurring agents which are capable of being delivered to muscle by the vasculature, crossing endothelial and basal lamina barriers, and being internalized by mature muscle fibers. Our long term goal is to identify and harness such agents so that gene delivery to muscle can be facilitated by these same factors. Our first specific aim characterizes naturally occurring ligands for receptor density in myogenic cells, muscle specificity, and cellular trafficking. The second specific aim pursues the alternative approach of the biopan screening of millions of random peptides for myogenic cell- specific surface binding via phage-display libraries which we have constructed. Peptides that show good binding characteristics are then further characterized. Our final aim takes a subset of the ligands identified in the first two aims, which show that most promising muscle targeting characteristics, and applies them for muscle cell targeting of enzyme complexes and neutral liposomes (LPDII). Our goal is to provide a database of potential targeting ligands which can be utilized for altered tropism viral vectors, or receptor-mediated gene or protein delivery. We feel this approach will facilitate approaches aimed at achieving systemic delivery of therapeutic genes and proteins to muscle tissue.